Inhibitory effects of purine and pyrimidine analogs usually involve a prior conversion of the analog to the phosphorylated derivative which may result in (1) incorporation into DNA resulting in genetic changes or hypersensitivity to x-ray or ultraviolet radiation, (2) inhibition of protein synthesis or formation of abnormal protein if it is incorporated into RNA or DNA, (3) interference with nucleotide interconversions at the substrate level such as the inhibition of thymidylate synthesis by 5-fluorodeoxyuridylic acid, (4) interferences with nucleotide cofactor functions such as those which result from incorporation of gluorouracil into UDPX compounds, (5) inhibition of transport or (6) the fraudulent nucleotides may exert feedback effects or enzyme repressions and inductions. Each of these effects can be studied in detail when the metabolic abnormality is known. The specific objectives of the proposed work center around studies of the above mechanisms involved in the inhibitory processes exerted by selected analogs. The transport of nucleosides, nucleoside analogs, purines and pyrimidines in Escherichia coli is being studied in detail. The specific objective of these studies is to provide information which is relevant to the transport of chemotherapeutic agents in animal cells.